Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.
An MS plaque is a focal area where myelin has been destroyed by inflammation, with variable injury to the axons running through it. Three processes define it: demyelination, inflammation, and axonal loss. Early lesions show myelin destruction with relative axonal preservation, while older lesions add irreversible axonal loss and scarring. This progression explains the two kinds of disability in MS. Relapse-related disability tracks with inflammation and demyelination, which can partly recover, while progressive disability tracks with axonal loss, which cannot.
Active versus chronic plaques
Active plaques are hypercellular. They contain foamy macrophages digesting myelin, reactive astrocytes, and perivenular inflammation, with active myelin breakdown advancing outward at the lesion edge. Because the blood-brain barrier is disrupted where inflammation is active, these lesions enhance with gadolinium on MRI.
Chronic plaques are sharply demarcated and hypocellular. The dominant feature is fibrillary gliosis, a glial scar, with axonal damage and loss and no active myelin breakdown. Mature oligodendrocytes are markedly reduced or absent, which is why chronic lesions remyelinate poorly even after inflammation subsides. Some perivascular inflammation may persist, and partial remyelination can sometimes be found at the edge.
Where plaques sit
Typical locations are the periventricular white matter, optic nerves and chiasm, corpus callosum, brainstem, cerebellum, and spinal cord, especially the cervical segment. The perivascular distribution follows from the outside-in pathogenesis: inflammatory cells arrive through small veins and spread outward along perivenular spaces. Gross examination in advanced disease may show brain atrophy with widened cortical sulci, enlarged ventricles, and mild spinal cord swelling with thickened meninges, all reflecting cumulative tissue loss.
Axonal injury begins early. Damaged axonal terminals and exposed neurofilaments are already visible during predominantly inflammatory phases, and neurodegeneration appears to precede the first clinical episode. Areas of so-called dirty-appearing white matter show diffuse myelin and axonal loss without forming discrete plaques, representing disease burden beyond the counted lesions.
Evidence anchors
- Lassmann H. Multiple sclerosis pathology. Cold Spring Harb Perspect Med. 2018;8(3):a028936. doi:10.1101/cshperspect.a028936
- Filippi M, Preziosa P, Banwell BL, et al. Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines. Brain. 2016;139(Pt 7):1858-1879. doi:10.1093/brain/aww144